D-Cycloserine (i.e., 4-amino-3-isoxazolidinone), is a natural product of Streptomyces orchidaceus and Streptomyces garyphalus, which acts as a competitive antagonist of D-alanine, one component of bacterial cell walls. D-cycloserine inhibits alanine racemase and alanine synthetase, accumulation of an incomplete cell wall component results in bacterial cell walls damaging. It has been known as an antibiotic drug since the late 1950s and marketed under a brand name Seromycin®. It was classified on the World Health Organization's List of Essential Medicines as a second-line drug for the treatment of multidrug-resistant tuberculosis (MDR-TB).
In addition, D-cycloserine can penetrate into the central nervous system (CNS), and it has a unique potential to target the glycine-binding site of N-methyl-D-aspartate (NMDA) receptors in humans. As a selective partial NMDA-agonist, it was later proven on slice preparations, that D-cycloserine influences long-term potentiation (LTP), a neuronal mechanism for learning processes. Interestingly, it acts as a positive modulator at the NMDA receptor at low dose, but as a negative modulator at high dose. Therefore, the use of D-cycloserine is limited due to its side effects including headaches, drowsiness, depression, dizziness, vertigo, confusion, paresthesia, dysarthria, hyperirritability, psychosis, convulsions, and shaking (tremors) when the dosing is inappropriate. Meanwhile, overdosing with D-cycloserine may result in paresis, seizures, and coma, in addition, alcohol consumption may increase the risk of seizures as well.
Since LTP is important for cognitive functions, D-cycloserine has been introduced to neuropsychiatric studies, with a proper dosage, to evaluate its therapeutic potentials for neurological and psychiatric conditions such as Alzheimer's disease, schizophrenia, depression, obsessive compulsive disorder, autism, post-traumatic stress disorder and anxiety disorders.